The overall goal of this three-year Transition Career Development Award (K22) is to develop my independent career in the epidemiology and prevention of prostate cancer, with a focus on nutrition, molecular epidemiology, and genetics. In May 2004, I started my first independent Assistant level position at the Fred Hutchinson Cancer Research Center with a joint appointment at the University of Washington. Prior to this position, I received training in nutrition and epidemiology at the University of Kiel, Germany and the University of North Carolina, and completed a post-doctoral fellowship at the National Cancer Institute where I worked on several research projects investigating nutritional and genetic risk factors of colorectal tumors. Despite my limited experience in prostate cancer, I decided to focus my future research on prostate cancer given our limited understanding about the etiology of this common disease. My environment at the FHCRC is excellent for studies in prostate cancer, due to the large, multidisciplinary faculty focused on prostate cancer research and access to many large epidemiologic studies investigating this disease. I will conduct my proposed research project "Selenium, Genetic Variation in Selenoenzymes, and Prostate Cancer" within the Prostate Cancer Prevention Trial (PCPT) a large trial that tested finasteride for prevention of prostate cancer. This trial provides an excellent resource for my study because it collected detailed lifestyle data and biological specimens. My long-term goal is to better understand the molecular and genetic pathways underlying selenium as a chemopreventive agent for prostate cancer. Selenium is required for the activity of selenoenzymes, which have important antioxidative properties that prevent oxidative damage to DNA and other biomolecules, and may also modulate inflammation and immune response. My K22 proposal consists of a combination of adequately powered studies (primary specific aims) and pilot studies (secondary specific aims) that will support a subsequent R01 application. Primary specific aims of my study will test whether a) genetic variation in selenoenzymes and b) lifestyle factors are associated with activity of selenoenzymes. In secondary specific aim 1, I will explore biomarkers of oxidative stress, inflammation, and immune response in relation to selenium levels and selenoenzyme activity. In secondary specific aim 2, I will explore the use of immortalized lymphocytes to study impact of genetic variants in selenoenzymes. [unreadable] [unreadable] Results of these studies will add information on the molecular and genetic pathways of selenium to improve our knowledge about the potential chemopreventive effect of selenium on prostate cancer and help to identify men who benefit most from selenium supplementation. This proposal will address key questions for understanding the eventual outcome of SELECT (Selenium and Vitamin E Cancer Prevention Trial), a very large prevention trial that is currently testing the effect of selenium on prostate cancer incidence. [unreadable] [unreadable]